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Biomedical subjects

T R Russell

Publications and source records attributed to T R Russell.

At least 55 records · Page 3Linked to original sources
PubMed1978

Modulation of granulopoiesis: opposing roles of prostaglandins F and E.

CSF-dependent myeloid colony growth can be augmented or inhibited by a number of modulating factors. PGs of the E series are known to inhibit colony formation. The antagonistic actions of PGE and PGF in many biological systems prompted us to compare their effects on myelopoiesis in vitro. PGF2alpha at an optimal concentration of 1 x 10(-9)M increased colony formation by 50% over that stimulated by CSF alone. Similar augmentation was also observed from 16,16-dimethyl PGF2alpha, PGF1alpha, 6-keto PGF1alpha, and MIX. In contrast PGE1, PGE2, and 15(S),15-methyl PGE1 inhibited colony growth. Simulation by PGF reflected an absolute increase in granulocytic colonies, whereas inhibition by PGE affected both granulocyte and macrophage colony formation. The relative levels of PGE and PGF may play a determining role in the modulation of granulopoiesis.

Animals↗
PubMed1977

Low rectovaginal fistulas. Approach and treatment.

Experience with thirty-two patients with a low rectovaginal fistula with or without attendant sphincter damage is reported. The technic used is advancement of the anterior rectal wall with excision of the infected anal glandular tissue and repair of muscle tissue when indicated. Anorectal infection and childbirth injuries were the common causes. An acceptable recurrence rate was achieved. Colostomy was not used in this series.

Adult↗
PubMed1976

Guanylate cyclase and cyclic guanosine 3':5'-monophosphate phosphodiesterase activities and cyclic guanosine 3':5'-monophosphate levels in normal and transformed fibroblasts in culture.

To investigate the role of guanosine 3':5'-monophosphate (cyclic GMP) in cultured cells we have measured guanylate cyclase and cyclic GMP phosphodiesterase activities and cyclic GMP levels in normal and transformed fibroblastic cells. Guanylate cyclase activity is found almost exclusively in the particulate fraction of normal rat kidney (NRK) and BALB 3T3 cells. Enzyme activity is stimulated 3- to 10-fold by treatment with the detergent Lubrol PX. However, enhancement of guanylate cyclase by fibroblast growth factor could not be demonstrated under a variety of assay conditions. In both NRK and BALB 3T3 cells guanylate cyclase activity is low during logarithmic growth and increases as the cells crowd together and growth slows. Guanylate cyclase activity is undetectable in homogenates of NRK cells transformed by the Kirsten sarcoma virus (KNRK cells) either in the presence or absence of Lubrol PX. Guanylate cyclase activity is also greatly decreased in NRK cells transformed by Moloney, Schmidt-Ruppin, or Harvey viruses. BALB 3T3 cells transformed by RNA viruses (Kirsten, Harvey, or Moloney), by a DNA virus (SV40), by methylcholanthrene, or spontaneously, all have diminished but readily detectable guanylate cyclase activity. Cyclic GMP phosphodiesterase activity is found predominately in the soluble fraction of NRK cells. This activity increases slightly as NRK cells enter the stationary growth phase. Cyclic GMP phosphodiesterase activity is undetectable in two clones of KNRK cells under a variety of assay conditions, and is decreased relative to the level present in NRK cells in a third KNRK clone. However, both Moloney- and Schmidt-Ruppin-transformed NRK cells have a phosphodiesterase activity similar to that found in NRK cells. Boiled supernatant from both NRK and KNRK cells is observed to appreciably enhance the activity of activator-deficient phosphodiesterase from bovine heart. This result indicates that the absence of cyclic GMP phosphodiesterase activity in KNRK cells is not due to a loss of the phosphodiesterase activator. The intracellular concentration of cyclic GMP is found to be very low in transformed NRK cells when compared to levels measured in confluent NRK cells. The low levels of cyclic GMP in transformed NRK cells reflect the greatly decreased guanylate cyclase activity observed in these cells. These results do not appear to support the suggestion that cyclic GMP promotes the growth of fibroblastic cells.

Cell Line↗
PubMed1976

Conversion of 3T3 fibroblasts into adipose cells: triggering of differentiation by prostaglandin F2alpha and 1-methyl-3-isobutyl xanthine.

Green and Kehinde [(1974) cell 1, 113-116] have isolated clones of Swiss 3T3 fibriblasts that are able to convert to adipose cells. In this paper we report on two chemicals (prostaglandin F2alpha, 0.1 mug ml, and 1-methyl-3-isobutyl xanthine, 0.5 mM) that are able to rapidly and irreversibly program the fibroblasts to differentiate into adipose cells. Confluent cultures treated with prostaglandin F2alpha and insulin for 3-5 days, followed by insulin alone for 7-48 hr, yield numerous adipocyte colonies compared to control dishes and dishes treated with insulin alone. Cells treated with prostaglandin F2alpha or 1-methyl-3-isobutyl xanthine alone, rinsed, and then exposed to insulin gave similar results, indicating that the continuous presence of the triggering agent is not required to elicit the conversion of the fibroblasts to adipocytes. Agents that raise intracellular levels of 3':5'-cyclic AMP. 1.0 mM; 8-bromo-cyclic AMP,0.5 mM; and prostaglandin E1, 0.1 mug/ml) do not trigger the conversion process, suggesting that cyclic AMP may not be the mediator of differentiation in these cells. 8-Bromo-cyclic AMP, however, does induce thase; 3':5'-nucleotidohydrolase; EC 3.1.4.17) in these cells; the induction appears to be mediated by increases in intracellular cyclic AMP levels. These results indicate that this cell line might offer a system for studying the regulation of a type of cellular differentiation.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1975

Cellular levels of feedback regulator of adenylate cyclase and the effect of epinephrine and insulin.

We have obtained direct evidence that shows the cellular formation and subsequent release of a potent inhibitor (feedback regulator) of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] by adipocytes, upon stimulation with epinephrine. The appearance of such a feedback regulator in adipocytes preceded its release into the medium. During a 30 min incubation, intracellular regulator levels rose rapidly and reached 39-61 units/g of adipocyte at 10 min. Release of inhibitor into the medium increased slowly and was 11-16 units/g of adipocyte at 10 min. Upon continued incubation, the cells at 30 min contained 30-41 units/g of ingibitor, slightly less than the content at 30 min; meanwhile, the medium content rose more than 3-fold. The inhibitor from both locations appeared to have the same characteristics, judging from the purification procedures and the biological activities on hormone-stimulated adenylate cyclase. Adenylate cyclase was inhibited by the feedback regulator in vitro when either epinephrine, corticotropin (ACTH), or glucagon was used as activator. The site of action of this inhibitor is therefore most likely beyond the specific hormone receptors. A new in vitro action of insulin has been found. Insulin, 50-500 microunits/ml, inhibited the formation and release of this factor from isolated rat or hamster adipocytes by 29-81% after these cells were stimulated by hormones that raise intracellular adenosine 3':5'-cyclic monophosphate. This factor enhaced the effect of insulin in lowering the adenosine 3':5'-cyclic monophosphate levels in fresh rat adipocytes. A reduced formation of such a factor may modify the metabolic events in adipocytes, and some as yet unexplained effects of insulin could therefore be linked to the metabolic effects of this factor.

Adenylyl Cyclases↗
PubMed1975

The choleretic mechanisms of sodium taurocholate, secretin, and glucagon.

Mongrel dogs were prepared by cholecystectomy, ligation of the lesser pancreatic duct, and insertion of modified Thomas cannulas into the duodenum and stomach. After recovery from surgery, experiments were performed by cannulation of the common bile duct for bile collection through the duodenal cannula. Bile flow and composition and the biliary clearance of erythritol were observed during secretin, glucagon, or sodium taurocholate choleresis and were compared with control studies. All test substances caused increased bile secretion. Sodium taurocholate caused a marked increase in bile salt output and in the biliary clearance of erythritol. Secretin caused a large increase in bile flow, no increase in bile salt output, and a very small increase in the biliary clearance of erythritol. The results indicate marked differences in the choleretic mechanism of sodium taurocholate and secretin and suggest that the principal action of taurocholate was on the canaliculi and the principal action of secretin was on the ducts.

Animals↗
PubMed1975

Inhibition of cyclic nucleotide phosphodiesterase activity by an endogenous factor.

Cyclic nucleotide phosphodiesterase activity of several tissues of rat is inhibited by an endogenous factor isolated from rat adipocytes following exposure of these cells to agents that raise intracellular cyclic AMP levels. The inhibitory action was demonstrated with varying cAMP concentrations from 0.1-400 muM. Enzyme from 10,000 X g supernatant of epididymal adipose tissue was inhibited approximately 2-3 fold more than the plasma membrane of adipocytes by a given concentration of the feedback regulator. Kinetic analysis of cAMP phosphodiesterase of plasma membrane showed that feedback regulator (8.8 U/ml) inhibited the Vmax 48%. The maximum inhibition of phosphodiesterase by feedback regulator (20 U/ml) was about 80%. The apparent Km for cAMP was increased. The ability of phosphodiesterase from several tissues of rat (10,000 X g supernatant) to hydrolyze cAMP and cGMP was tested. Feedback regulator inhibited cGMP hydrolysis in cardiac muscle and 5 other tissues 23-92% more than it inhibited the hydrolysis of cAMP. The physiological significance of this inhibitory effect can begin to be clarified when the feedback regulator is purified to homogeneity and characterized.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1973

Interrelationship between adenylate cyclase activity, adenosine 3':5' cyclic monophosphate phosphodiesterase activity, adenosine 3':5' cyclic monophosphate levels, and growth of cells in culture.

To investigate how cell population density influences the intracellular concentration of cyclic AMP we have measured adenylate cyclase and cyclic AMP phosphodiesterase activities and cyclic AMP levels at various stages of cell density in normal rat-kidney (NRK) cells, which exhibit contact-inhibition of growth, and in normal chick-embryo fibroblasts (CEF), which do not show contact inhibition of growth under our conditions. Until NRK cells reach confluency, both activities increase with increasing cell population and cyclic AMP levels are low. As NRK cells reach confluency, cyclic AMP phosphodiesterase activity decreases somewhat whereas adenylate cyclase activity continues to rise. This increase in synthetic ability is accompanied by the increase in cyclic AMP levels which occurs in these cells at confluency. In CEF grown in 5% serum where density-dependent inhibition of growth is not observed, both adenylate cyclase and cyclic AMP phosphodiesterase activities increase proportionately with increasing cell population density. No significant alteration occurs in the ratio between these two enzyme activities and no change is observed in cyclic AMP levels. The NaF-stimulated activity in NRK cells increases with increasing cell density until the cells reach confluency; thereafter the NaF-stimulated activity remains constant. In contrast, the NaF-stimulated activity observed in CEF does not vary appreciably between light and heavy density. The observed changes in the enzymes of cyclic AMP metabolism accurately reflect the changes in cyclic AMP concentration as a function of cell population density. The data indicate that these two enzyme activities respond to increasing cell density to elicit a rise in intracellular cyclic AMP levels. The elevated cyclic AMP levels are thought to be involved in the regulation of cellular growth rate and the mediation of contact inhibition of growth.

Adenylyl Cyclases↗